Our project investigates the mechanisms by which fetal trophoblast cells invade and modify the walls of the spiral arteries supplying the placenta. Adequate invasion and remodeling provide for a normal blood supply at the placenta. Inadequate invasion has been associated with hypertensive pregnancies, pre-eclampsia, intrauterine growth retardation and other problems. We use the macaque model since it is one of the few species available that has artery invasion similar to that in the human. The studies also utilize the same material to analyze placental growth and differentiation in general. During the past year we have made significant progress in a number of areas. In 1994 we completed a light and electron microscopic study of the development of a thick basement membrane-like structure in the anchoring villi of the macaque placenta. This structure appears to be important in isolating fetal connective tissue elements from maternally-derived cells. We also completed and published a study demonstrating the presence of a 72 KD type IV collagenase at sites where the invasive trophoblast cells migrate into the wall of the spiral arteries. We also completed and published a study of growth and development of the chorionic plate of the macaque placenta and related it to placental growth in general. Finally, we completed and published an immunocytochemical study examining cell proliferation in various compartments of macaque placentas using antibodies to two nuclear proteins KI-67 and puna. This enabled us to demonstrate that the arterial trophoblast cells were non-proliferative and therefore must all migrate to this site from elsewhere. Preliminary studies have begun on expression of various adhesion molecules in the arteries, including integrins, n-cam and others as well as the appearance of various extracellular matrix molecules in the arterial wall.